Fibronectin: An Interesting Vocal Fold Protein

A great deal of information is accruing regarding the function of the extracellular matrix. Once thought to be simply a structural entity to surround cells, it is now known to do much more. Fibronectin in particular has received specific attention. Fibronectin is a ubiquitous glycoprotein found most abundantly in the extracellular matrix of regenerating, healing, and embryonic tissue. Vast evidence supports the fact that fibronectin participates in many diverse functions throughout the body that are relevant to vocal fold biology. This article introduces the structure of fibronectin and its isoforms and provides an introduction to some of the many functions it plays. It also reviews the evidence about fibronectin's place in vocal folds and vocal fold pathology. It discusses fibronectin's presence in vocal nodules, vocal polyps, vocal scarring, and Reinke's edema, and reviews the data on its role in mucosal wave impairment. Lastly, it discusses preliminary microarray data that show gene expression for fibronectin to be upregulated in true vocal folds when compared to false vocal folds.     

Short-Term Therapeutic Trial of Proton Pump Inhibitors in Suspected Extraesophageal Reflux

Pharyngoesophageal gastric acid reflux is thought to initiate chronic posterior laryngitis. The gold standard for measuring gastric reflux is dual-channel 24-hour pH monitoring. This is a time-consuming, inconvenient, expensive method that is not available in all areas. New therapeutic regimes that make use of proton pump inhibitors (PPIs) have proven to be therapeutically efficient for control of acid reflux. Twenty-four consecutive patients with chronic voice disorders and signs of posterior laryngitis were selected for therapy. Twenty-four hour pH monitoring was performed independently before the therapy. The trial therapy consisted of all patients receiving pantoprazole, 40 mg once daily for 6 weeks. Immediately following the therapy a statistically significant (p < 0.05) improvement was observed in all patients. This improvement was analyzed retrospectively by comparison with the results of 24-hour pH monitoring. In 71% of the patients the 24-hour pH-monitoring gave a positive result showing a high number of patients with extraesophageal reflux in our study group. Patients with positive results of pH-monitoring responded in a statistically significant manner (p < 0.05) to the pantoprazole therapy, whereas those patients without detected reflux did not. A 3-month follow-up of the patients with a positive result of the pH-monitoring confirmed the improvement. No patients reported adverse effects. A 6-week treatment with pantoprazole can be clinically justified. It helps to save time and reduce costs, allows for selection of reflux-negative patients for alternative therapy, and may prevent inadequate treatment of patients with false-negative pH monitoring. Twenty-four hour pH monitoring is still recommended for patients unresponsive to this trial therapy.     

Excitation transfer induced spectral diffusion and the influence of structural spectral diffusion

The theory of vibrational excitation transfer, which causes spectral diffusion and is also influenced by structural spectral diffusion, is developed and applied to systems consisting of vibrational chromophores. Excitation transfer induced spectral diffusion is the time-dependent change in vibrational frequency induced by an excitation on an initially excited molecule jumping to other molecules that have different vibrational frequencies within the inhomogeneously broadened vibrational absorption line. The excitation transfer process is modeled as Fo?rster resonant transfer, which depends on the overlap of the homogeneous spectra of the donating and accepting vibrational chromophores. Because the absorption line is inhomogeneously broadened, two molecules in close proximity can have overlaps of their homogeneous lines that range from substantial to very little. In the absence of structural dynamics, the overlap of the homogeneous lines of the donating and accepting vibrational chromophores would be fixed. However, dynamics of the medium that contains the vibrational chromophores, e.g., a liquid solvent or a surrounding protein, produce spectral diffusion. Spectral diffusion causes the position of a molecule's homogeneous line within the inhomogeneous spectrum to change with time. Therefore, the overlap of donating and accepting molecules' homogeneous lines is time dependent, which must be taken into account in the excitation transfer theory. The excitation transfer problem is solved for inhomogeneous lines with fluctuating homogeneous line frequencies. The method allows the simultaneous treatment of both excitation transfer induced spectral diffusion and structural fluctuation induced spectral diffusion. It is found that the excitation transfer process is enhanced by the stochastic fluctuations in frequencies. It is shown how a measurement of spectral diffusion can be separated into the two types of spectral diffusion, which permits the structural spectral diffusion to be determined in the presence of excitation transfer spectral diffusion. Various approximations and computational methodologies are explored.     

Intersystem crossing from singlet states of molecular dimers and monomers in mixed molecular crystals: picosecond stimulated photon echo experiments

An experimental study of the excited-state dynamics of pentacene dimers and monomers in p-terphenyl host crystals is presented. Picosecond stimulated photon echoes, picosecond photon echoes, and fluorescence lifetime measurements are used to study intersystem crossing and homogeneous dephasing of delocalized dimers and monomers at 1.8 K. It is found that the dimer states can have intersystem crossing rate constants which are orders of magnitude greater than the corresponding monomers. Three mechanisms are considered to explain the differences between dimer and monomer intersystem crossing. Fluorescence lifetime measurements and photon echo measurements demonstrate that the only source of homogeneous line broadening at 1.8 K is population relaxation. These measurements combined with the stimulated echo measurements show that differences in lifetimes exhibited by the various dimer and various monomer sites are due solely to differences in intersystem crossing rate constants.     

Electrophysiologic monitoring of the recurrent laryngeal nerves may not predict bilateral vocal fold immobility after thyroid surgery

Two cases of bilateral vocal fold immobility (VFI) after identification and preservation of the recurrent laryngeal nerves (RLNs) required tracheotomy until vocal fold recovery. The first patient underwent thyroid surgery without preoperative or postoperative evaluation of the vocal folds, administration of postoperative intravenous steroids, or electrophysiologic monitoring of the RLNs, whereas the second patient underwent a thyroid procedure in which all of the aforementioned were executed. Preoperative and postoperative clinical evaluation of the RLNs is strongly suggested in patients undergoing thyroid surgery, especially revision surgery. Patients potentially undergoing total thyroidectomy should be counseled about the remote chance of airway obstruction and should be properly selected for this operation. Subclinical stretching of the RLNs or ischemia from the endotracheal tube cuff can result in unilateral VFI, and rarely bilateral VFI, requiring reintubation, tracheotomy, or vocal fold lateralization. Electrophysiologic monitoring may not always predict bilateral VFI.     

Dynamics of nanoscopic water: vibrational echo and infrared pump-probe studies of reverse micelles

The dynamics of water in nanoscopic pools 1.7-4.0 nm in diameter in AOT reverse micelles were studied with ultrafast infrared spectrally resolved stimulated vibrational echo and pump-probe spectroscopies. The experiments were conducted on the OD hydroxyl stretch of low-concentration HOD in the H2O, providing a direct examination of the hydrogen-bond network dynamics. Pump-probe experiments show that the vibrational lifetime of the OD stretch mode increases as the size of the reverse micelle decreases. These experiments are also sensitive to hydrogen-bond dissociation and reformation dynamics, which are observed to change with reverse micelle size. Spectrally resolved vibrational echo data were obtained at several frequencies. The vibrational echo data are compared to data taken on bulk water and on a 6 M NaCl solution, which is used to examine the role of ionic strength on the water dynamics in reverse micelles. Two types of vibrational echo measurements are presented: the vibrational echo decays and the vibrational echo peak shifts. As the water nanopool size decreases, the vibrational echo decays become slower. Even the largest nanopool (4 nm, approximately 1000 water molecules) has dynamics that are substantially slower than bulk water. It is demonstrated that the slow dynamics in the reverse micelle water nanopools are a result of confinement rather than ionic strength. The data are fit using time-dependent diagrammatic perturbation theory to obtain the frequency-frequency correlation function (FFCF) for each reverse micelle. The results are compared to the FFCF of water and show that the largest differences are in the slowest time scale dynamics. In bulk water, the slowest time scale dynamics are caused by hydrogen-bond network equilibration, i.e., the making and breaking of hydrogen bonds. For the smallest nanopools, the longest time scale component of the water dynamics is approximately 10 times longer than the dynamics in bulk water. The vibrational echo data for the smallest reverse micelle displays a dependence on the detection wavelength, which may indicate that multiple ensembles of water molecules are being observed.     

Four novel spirooxazacamphorsultam derivatives

The chiral compounds (6aS,9S,10aR)‐11,11‐dimethyl‐5,5‐dioxo‐2,3,8,9‐tetrahydro‐6H‐6a,9‐methanooxazaolo[2,3‐i][2,1]benzisothiazol‐10(7H)‐one, C₁₂H₁₇NO₄S, (1), (7aS,10S,11aR)‐12,12‐dimethyl‐6,6‐dioxo‐3,4,9,10‐tetrahydro‐7H‐7a,10‐methano‐2H‐1,3‐oxazino[2,3‐i][2,1]benzisothiazol‐11(8H)‐one, C₁₃H₁₉NO₄S, (2), (6aS,9S,10R,10aR)‐11,11‐dimethyl‐5,5‐dioxo‐2,3,7,8,9,10‐hexahydro‐6H‐6a,9‐methanooxazolo[2,3‐i][2,1]benzisothiazol‐10‐ol, C₁₂H₁₉NO₄S, (3), and (7aS,10S,11R,11aR)‐12,12‐dimethyl‐6,6‐dioxo‐3,4,8,9,10,11‐hexahydro‐7H‐7a‐methano‐2H‐[1,3]oxazino[2,3‐i][2,1]benzisothiazol‐11‐ol, C₁₃H₂₁NO₄S, (4), consist of a camphor core with a five‐membered spirosultaoxazolidine or six‐membered spirosultaoxazine, as both their keto and hydroxy derivatives. In each structure, the molecules are linked via hydrogen bonding to the sulfonyl O atoms, forming chains in the unit‐cell b‐axis direction. The chains interconnect via weak C—H...O interactions. The keto compounds have very similar packing but represent the highest melting [507–508 K for (1)] and lowest melting [457–458 K for (2)] solids.     

Testing the core/shell model of nanoconfined water in reverse micelles using linear and nonlinear IR spectroscopy

A core/shell model has often been used to describe water confined to the interior of reverse micelles. The validity of this model for water encapsulated in AOT/isooctane reverse micelles ranging in diameter from 1.7 to 28 nm (w0 = 2-60) and bulk water is investigated using four experimental observables: the hydroxyl stretch absorption spectra, vibrational population relaxation times, orientational relaxation rates, and spectral diffusion dynamics. The time dependent observables are measured with ultrafast infrared spectrally resolved pump-probe and vibrational echo spectroscopies. Major progressive changes appear in all observables as the system moves from bulk water to the smallest water nanopool, w0 = 2. The dynamics are readily distinguishable for reverse micelle sizes smaller than 7 nm in diameter (w0 = 20) compared to the response of bulk water. The results also demonstrate that the size dependent absorption spectra and population relaxation times can be quantitatively predicted using a core-shell model in which the properties of the core (interior of the nanopool) are taken to be those of bulk water and the properties of the shell (water associated with the headgroups) are taken to be those of w0 = 2. A weighted sum of the core and shell components reproduces the size dependent spectra and the nonexponential population relaxation dynamics. However, the same model does not reproduce the spectral diffusion and the orientational relaxation experiments. It is proposed that, when hydrogen bond structural rearrangement is involved (orientational relaxation and spectral diffusion), dynamical coupling between the shell and the core cause the water nanopool to display more homogeneous dynamics. Therefore, the absorption spectra and vibrational lifetime decays can discern different hydrogen bonding environments whereas orientational and spectral diffusion correlation functions predict that the dynamics are size dependent but not as strongly spatially dependent within a reverse micelle.     

A mode coupling theory description of the short- and long-time dynamics of nematogens in the isotropic phase

Optical heterodyne-detected optical Kerr effect (OHD-OKE) experimental data are pre-sented on nematogens 4-(trans-4-n-octylcyclohexyl)isothiocyanatobenzene (8-CHBT), and 4-(4-pentyl-cyclohexyl)-benzonitrile (5-PCH) in the isotropic phase. The 8-CHBT and 5-PCH data and previously published data on 4-pentyl-4-biphenylcarbonitrile (5-CB) are analyzed using a modification of a schematic mode coupling theory (MCT) that has been successful in describing the dynamics of supercooled liquids. At long time, the OHD-OKE data (orientational relaxation) are well described with the standard Landau-de Gennes (LdG) theory. The data decay as a single exponential. The decay time diverges as the isotropic to nematic phase transition is approached from above. Previously there has been no theory that can describe the complex dynamics that occur at times short compared to the LdG exponential decay. Earlier, it has been noted that the short-time nematogen dynamics, which consist of several power laws, have a functional form identical to that observed for the short time behavior of the orientational relaxation of supercooled liquids. The temperature-dependent orientational dynamics of supercooled liquids have recently been successfully described using a schematic mode coupling theory. The schematic MCT theory that fits the supercooled liquid data does not reproduce the nematogen data within experimental error. The similarities of the nematogen data to the supercooled liquid data are the motivation for applying a modification of the successful MCT theory to nematogen dynamics in the isotropic phase. The results presented below show that the new schematic MCT theory does an excellent job of reproducing the nematogen isotropic phase OHD-OKE data on all time scales and at all temperatures.     

Photoinduced electron transfer and geminate recombination in the group head region of micelles

A pump-probe spectroscopic study of photoinduced forward electron transfer and geminate recombination between donors and acceptors located in the head group regions of micelles is presented. The hole donor is octadecyl-rhodamine B (ODRB) and the hole acceptor is N,N-dimethyl-aniline (DMA). The experiments are conducted as a function of the DMA concentration in the dodecyltrimethylammonium bromide and tetradecyltrimethylammonium bromide micelles. In spite of the fact that the absorptions of both the ODRB radical and ground state bleach spectrally overlap with the ODRB excited state absorption, a procedure that makes it possible to determine the geminate recombination dynamics is presented. These experiments are the first to measure the dynamics of geminate recombination in micelles, and the experiments have two orders of magnitude better time resolution than previous studies of forward transfer. The experimental data are compared to statistical mechanics theoretical calculations of both the forward transfer and the geminate recombination. The theory includes important aspects of the topology of the micelle and the diffusion of the donor-acceptors in the micelle head group region. A semiquantitative but nonquantitative agreement between theory and experiments is achieved.